Basic Concepts Flashcards
What is a locus?
Segment of DNA occupying a particular position or location on a chromosome
What are alleles?
Alternative variants of a gene
- Wild type or common allele: single prevailing allele present in the majority of individuals
- Other versions are variant of mutant alleles that differ from the wild-type because of the presence of a mutation
Define the following:
- Homozygous
- Heterozygous
- Compound heterozygote
- Homozygous: when a person has a pair of identical alleles at a locus
- Heterozygous (aka “carrier”): when a person has different alleles on both pairs of a chromosome
- Compound heterozygote (aka “double heterozygote”): 2 different mutant alleles of the same gene are present
What is hemizygous?
Male has an abnormal allele for a gene located on the X chromsome and there is no other copy of the gene (neither homozygous nor heterozygous)
Genotype vs. phenotype?
- Genotype: set of alleles that make up his/her genetic constitution; either collectively at all loci or more typically, at a single locus
- Phenotype: observable expression of a genotype as a morphological, clinical, cellular, or biochemical trait
- Can be normal or abnormal
How many genes do humans have?
- Chromosomes?
- About 20,000 genes
- 46 chromosomes (23 pairs)
Describe the following genetic disorder patterns:
- Single gene (Menelian)
- Chromosomal
- Multifactorial
in terms of:
- Prevalence
- Pattern of inheritance
- Risk to relatives
Single gene (Mendelian)
- Numerous though individually rare
- Clear pattern of inheritance
- High risk to relatives
Chromsomal
- Mostly rare
- No clear pattern of inheritance
- Usually low risk to relatives
Multifactorial
- Common disorders
- No clear pattern of inheritance
- Low/moderate risk to relatives
What is penetrance?
Percentage of relatives expressing the disorder to any degree, from the most trivial to the most severe
What are different types/expressions of penetrance? Examples?
Age dependent penetrance
- Huntington disease
Incomplete penetrance: not all mutation carriers will manifest the disorder during a natural lifespan
- Lynch syndrome
What is expressivity?
Variation in the severity of a disorder in individuals who have inherited the same disease alleles
What are the different types/expressions of expressivity?
- Interfamilial variation: difference in severity between families
- Intrafamilial variation: difference in severity within families carrying the same mutation
- E.g. tuberous sclerosis
What is mosaicism? Subtypes?
Somatic mosaicism:
- A new mutation arising at an early stage in embryogenesis causing a partial phenotype
- Ex) segmental NF1
Gonadal/germline mosaicism:
- A new mutation arising during oogenesis or spermatogenesis may cause no phenotype in the parent but can be transmitted to the offspring
Describe autosomal dominant inheritance
- Number of mutant alleles
- Chance of passing to offspring
- Features of inheritance pattern
- 1 mutant allele is sufficient to cause disease
- 50% chance of transmission with each pregnancy
Features:
- Vertical transmission
- Male-to-male transmission
- Affected males = affected females
What inheritance pattern is seen here?
Typical autosomal dominant
What inheritance pattern is seen here?
Non-penetrance of autosomal dominant
What inheritance pattern is seen here?
New mutation (of autosomal dominant)
What inheritance pattern is seen here?
Sex-limited expression (of autosomal dominant)
What inheritance pattern is seen here?
Gonadal mosaicism
Describe autosomal recessive inheritance
- Number of mutant alleles
- Features of inheritance pattern
- 2 mutant genes are required to cause disease
Features:
- Horizontal pattern of affected individuals
- Males and females equally affected
- Parents unaffected yet obligate carriers
- Child of affected persons is (at least) obligate carrier
What is the Lyon Hypothesis?
One X in female somatic cells undergoes random inactivation
Describe sex chromosome inheritance
- Males are hemizygous for genes on the X chromosome
- All daughters of affected males are carriers
- 50% of daughters of carrier females are carriers
- 50% of sons of carrier females are affected
- All sons of affected males are “normal”; there is no male-male transmission of X linked conditions!
Describe the mitochondrial genome
- Linear vs. circular
- Number of nucleotides/genes
- Products
- Inheritance pattern
- Circular, mtDNA
- 16,000 nucleotides encoding 13 proteins (many are subunits of protein complexes of the respiratory chain, 2 rRNA genes, and 22 tRNA genes)
- Almost entire genome is coding sequence
- Derived from oocyte mitochondria, thus they exhibit MATRILINEAL inheritance
- Affected female can pass disorder to ALL of her progeny
- Expression determined by degree of heteroplasmy
What is multfactorial/polygenic inheritance?
Disorders/traits that result from complex interactions between many or few genes and the environment
- Although the disorder/trait may be familial, there is NOT a simple mendelian pattern of inheritance
- Recurrence risks are based on empiric data
What does this pedegree show?
Multifactorial inheritance
